Hybrid biosensors
First Claim
1. An apparatus comprising:
- a monolithic device including an array of planar microelectrodes disposed on a substrate, the array of microelectrodes being connected to a conductive pattern having contact points connected thereto;
a cell culture chamber in which the integrated device is disposed, the cell culture chamber being configured to contain a medium for cultured cells in a volume surrounding the respective surfaces of the microelectrodes, wherein cells are introduced into the cell culture chambers and a portion of the cells adhere to respective surfaces of the microelectrodes,wherein the diameter of a cell is larger than the diameter of a microelectrode;
a reference electrode disposed within the cell culture chamber;
means electrically connected to the contact points connected to the array of microelectrodes for selectively applying an electrical signal between each of the microelectrodes and the reference electrode;
means for detecting signals resulting from the application of the signal between each of the microelectrodes and the reference electrode;
a phase detector electrically connected to the signal detecting means; and
means for monitoring characteristics of cells which adhere to the respective surfaces of the microelectrodes based on impedance values derived from the resulting signals, the characteristics being selected from the group consisting of impedance, action potential parameters, cell membrane capacitance, cell membrane conductance, and cell/substrate seal resistance.
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Accused Products
Abstract
The invention relates to an apparatus and method for monitoring cells and to a method for monitoring changes in cells upon addition of an analyte to the cell'"'"'s environment, comprising a device which includes an array of microelectrodes disposed in a cell culture chamber, upon which array a portion of cells adhere to the surfaces of the microelectrodes. The diameter of the cells are larger than the diameters of the microelectrodes. A voltage signal is applied across each of the microelectrodes and a reference electrode. Detection and monitoring of the signals resulting from the application of the voltage signal provides information regarding the electrical characteristics of the individual cells, including impedance (combined cell membrane capacitance and conductance), action potential parameters, cell membrane capacitance, cell membrane conductance, and cell/substrate seal resistance. Such an invention is useful in detecting or screening a variety of biological and chemical agents.
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Citations
30 Claims
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1. An apparatus comprising:
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a monolithic device including an array of planar microelectrodes disposed on a substrate, the array of microelectrodes being connected to a conductive pattern having contact points connected thereto; a cell culture chamber in which the integrated device is disposed, the cell culture chamber being configured to contain a medium for cultured cells in a volume surrounding the respective surfaces of the microelectrodes, wherein cells are introduced into the cell culture chambers and a portion of the cells adhere to respective surfaces of the microelectrodes, wherein the diameter of a cell is larger than the diameter of a microelectrode; a reference electrode disposed within the cell culture chamber; means electrically connected to the contact points connected to the array of microelectrodes for selectively applying an electrical signal between each of the microelectrodes and the reference electrode; means for detecting signals resulting from the application of the signal between each of the microelectrodes and the reference electrode; a phase detector electrically connected to the signal detecting means; and means for monitoring characteristics of cells which adhere to the respective surfaces of the microelectrodes based on impedance values derived from the resulting signals, the characteristics being selected from the group consisting of impedance, action potential parameters, cell membrane capacitance, cell membrane conductance, and cell/substrate seal resistance. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
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30. An apparatus comprising:
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a monolithic device that includes an array of planar microelectrodes disposed on a substrate, the array of microelectrodes being connected to a conductive pattern having contacts points connected thereto; a cell culture chamber in which the monolithic device is disposed, the cell culture chamber being configured to contain a medium for cultured cells in a volume surrounding the respective surfaces of the microelectrodes, wherein cells are introduced into the cell culture chamber and a portion of the cells adhere to respective surfaces of the microelectrodes, wherein the diameter of a cell is larger than the diameter of a microelectrode; a reference electrode disposed within the cell culture chamber; means for selectively applying an electrical signal between each microelectrode and the reference electrode; means for detecting signals resulting from the application of the signal between the microelectrodes and the reference electrode; means for processing the detected signals across a spectrum of frequencies to calculate the impedance spectrum of each microelectrode.
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Specification